| Literature DB >> 30185550 |
Kim R Kampen1,2, Frank J G Scherpen3, Hasan Mahmud3, Arja Ter Elst3, André B Mulder4, Victor Guryev5, Han J M P Verhagen6, Kim De Keersmaecker2, Linda Smit6, Steven M Kornblau7, Eveline S J M De Bont1.
Abstract
High expression of VEGFC predicts adverse prognosis in acute myeloid leukemia (AML). We therefore explored VEGFC-targeting efficacy as an AML therapy using a VEGFC mAb. VEGFC antibody therapy enforced myelocytic differentiation of clonal CD34+ AML blasts. Treatment of CD34+ AML blasts with the antibody reduced expansion potential by 30% to 50% and enhanced differentiation via FOXO3A suppression and inhibition of MAPK/ERK proliferative signals. VEGFC antibody therapy also accelerated leukemia cell differentiation in a systemic humanized AML mouse model. Collectively, these results define a regulatory function of VEGFC in CD34+ AML cell fate decisions via FOXO3A and serve as a new potential differentiation therapy for patients with AML.Significance: These findings reveal VEGFC targeting as a promising new differentiation therapy in AML. Cancer Res; 78(20); 5940-8. ©2018 AACR. ©2018 American Association for Cancer Research.Entities:
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Year: 2018 PMID： 30185550 DOI： 10.1158/0008-5472.CAN-18-0250
Source DB: PubMed Journal: Cancer Res ISSN： 0008-5472 Impact factor: 12.701